The α-emitting radionuclides chelated to antibodies can give a high degree of tumoricidal activity. In radioimmunotherapy, α-emitting nuclides have been used for the treatment of leukemia and highly vascular tumors. When administered to a patient, the antibody attaches to the cancer cell and delivers a lethal radiation dose while sparing the surrounding healthy tissue. This is due to the short penetration range (40-100 μm) and high linear energy transfer in tissue of alpha particles from natural decay of α-emitting radionuclides.
In recent years, 212Bi (half life=60.6 min) has been considered to be the α-emitter of choice. 212Bi has been successfully used for radioimmunotherapy studies of leukemic mice, and human trials are currently underway. One disadvantage of 212Bi is the shielding requirements that arise from the 2.26 MeV γ-ray of the 212Bi daughter, 208Tl. However, 213Bi (T1/2=45.6 min) can be used as an alternative to 212Bi. 213Bi has less intense γ-ray emission, emitting a 440 keV γ-ray. Due to its lower energy, it may generate images comparable to 131I. The initial clinical trials in patients with acute myeloid leukemia have demonstrated the effectiveness of the alpha emitter 213Bi in killing cancer cells (Jurcic et al, 2002). Recent preclinical studies have also demonstrated the potential application of 213Bi in a variety of cancer systems and targeted radiotherapy.
213Bi is currently available through a 225Ac/213Bi generator. The generator uses a cation-exchange resin BioRad® MP-50 (U.S. Pat. No. 6,603,127, issued Aug. 5, 2003) which has been used in the past in 224Ra/212Bi generator systems. This generator failed to function after a few days when large amounts (20 mCi) of 225Ac were loaded onto the generator. The organic-based resins are not stable in high radiation field and due to radiolysis they breakdown resulting in an increase in 225Ac breakthrough and flow restriction. An alternative generator that has been used in the past is a two-stage silica-based extraction system (Wu et. al., 1997), but it is time consuming and gives a low bismuth yield. Therefore, ion exchange generator systems are needed that possess higher radiation stability, faster mass transfer, increased yield and purity, demonstrate selectivity with low Ac breakthrough and have a higher capacity.